Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0 includes N1C);

Presence of deficient (d) DNA mismatch repair (dMMR). MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR. dMMR may be determined either locally or by site-selected reference lab. Note: loss of MLH1 and PMS2 commonly occur together. Formalin-fixed paraffin-embedded (FFPE) tumor tissue is required for subsequent retrospective central confirmation of dMMR status;

Patients with testing that did not show dMMR (loss of MMR protein) are not eligible to participate. Patients whose tumors show MSI-H by polymerase chain reaction (PCR)-based assay are not eligible to participate unless they also have MMR testing by IHC and are found to have dMMR (i.e. loss of one or more MMR proteins);

Patients who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) are eligible to participate;

Tumors must have been completely resected. In patients with tumor adherent to adjacent structures, en bloc R0 resection must be documented. Positive radial margins are not excluded as long as en bloc resection was performed. Proximal or distal margin positivity is excluded;

Absolute neutrophil count (ANC) >= 1500 mm^3;

Platelet count >= 100,000 mm^3; platelets >= 75,000 required for patients who received cycle 1 of mFOLFOX6 prior to registration;

Age \>= 12 years

Performance Status:

Patients \< 16 years of age: Lansky \>= 50%

Patients 16 to \< 18 years of age: Karnofsky \>= 50%

Patients \>= 18 years of age: Eastern Cooperative Oncology Group (ECOG) performance status =\< 2

This study involves: 1) an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown; and 2) an agent that has known genotoxic, mutagenic, and teratogenic effects; therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required; a female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)

Absolute neutrophil count (ANC) \>= 1500 mm\^3

Platelet count \>= 100,000 mm\^3; platelets \>= 75,000 required for patients who received cycle 1 of mFOLFOX6 prior to registration

Creatinine =\< 1.5 x upper limit of normal (ULN) or

Calculated creatinine clearance \>= 45 mL/min by Cockcroft-Gault equation

Alternatively, for patients \< 18 years of age, maximum serum creatinine =\< the below age-gender-specific norms:

12 years: 1.2 (male and female)

13 to \< 16 years: 1.5 (male), 1.4 (female)

16 to \< 18 years: 1.7 (male), 1.4 (female)

Total bilirubin =\< 1.5 x upper limit of normal (ULN) except in the case of Gilbert disease

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)

Contact site personnel for more study details;

No evidence of residual involved lymph node disease or metastatic disease at the time of registration based on clinician assessment of imaging. The treating physician will determine if incidental lesions on imaging require workup to exclude metastatic disease. If based on review of images, the treating physician determines the patient to be stage III, then the patient is eligible;

No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for colon cancer except for one cycle of mFOLFOX6;

No active known autoimmune disease, including colitis, inflammatory bowel disease (i.e. ulcerative colitis or Crohn's disease), rheumatoid arthritis, panhypopituitarism, adrenal insufficiency;

No known active hepatitis B or C;

No other planned concurrent investigational agents or other tumor directed therapy (chemotherapy, radiation) while on study;

No systemic daily treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of registration;

No known history of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins;

No known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation;

No known allergy to 5-fluorouracil, oxaliplatin, or leucovorin;

Patients with testing that did not show dMMR (loss of MMR protein) are not eligible to participate; patients whose tumors show MSI-H by PCR-based assay are not eligible to participate unless they also have MMR testing by IHC and are found to have dMMR (i.e. loss of one or more MMR proteins)

Excluded if known active pulmonary disease with hypoxia defined as:

Oxygen saturation \< 85% on room air, or

Oxygen saturation \< 88% despite supplemental oxygen

Contact site personnel for more study details;

• Oncology (Pediatrics)

• Antibodies, Monoclonal

• Antimetabolites

• Atezolizumab

• Bone Density Conservation Agents

• Calcium

• Calcium, Dietary

• Calcium-Regulating Hormones and Agents

• Colonic Diseases

• Colonic Neoplasms

• Colorectal Neoplasms

• Colorectal Neoplasms, Hereditary Nonpolyposis

• Digestive System Diseases

• Digestive System Neoplasms

• DNA Repair-Deficiency Disorders

• Fluorouracil

• Folic Acid

• Gastrointestinal Diseases

• Gastrointestinal Neoplasms

• Genetic Diseases, Inborn

• Intestinal Diseases

• Intestinal Neoplasms

• Leucovorin

• Levoleucovorin

• Metabolic Diseases

• Molecular Mechanisms of Pharmacological Action

• Neoplasms

• Neoplasms by Site

• Neoplastic Syndromes, Hereditary

• Oxaliplatin

• Physiological Effects of Drugs

• Oncology (Adult)

• National Cancer Institute (NCI)