TAS-102 and Oxaliplatin for the Treatment of Refractory Stage IV Colon Cancer

Inclusion Criteria: * Histologically confirmed stage IV colon cancer (American Joint Committee on Cancer \[AJCC\] 7th edition) that has progressed after standard therapy that included fluorouracil (5-FU), irinotecan, oxaliplatin, bevacizumab (unless contraindicated) and an anti-EGFR antibody, if RAS wild type. Patients who could not tolerate standard agents because of unacceptable, but reversible toxicity necessitating their discontinuation will be allowed to participate * Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen * Progression of disease must be documented on the most recent scan * Presence of measurable disease * RAS mutation and mismatch repair deficiency (MMR) status must be determined (or tissue availability for testing if not already determined) * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Life expectancy of at least 3 months * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Hemoglobin \>= 9 g/dL * Platelets (PLT) \>= 75 x 10\^9/L * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 5 x upper limit of normal (ULN) * Adequate contraception if applicable * Women who are nursing and discontinue nursing prior to enrollment in the program * Ability to take oral medication (i.e., no feeding tube) * Patient able and willing to comply with study procedures as per protocol * Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures Exclusion Criteria: * Patients who have previously received TAS-102 * Grade 2 or higher peripheral neuropathy (functional impairment) * Symptomatic central nervous system (CNS) metastases requiring treatment * Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer) * Pregnancy or breast feeding * Current therapy with other investigational agents * Active infection with body temperature \>= 38 degree Celsius (C) due to infection * Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration) * Any anticancer therapy within prior 3 weeks of first dose of study drug * History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102 * Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior 4 weeks * Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication * Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse (CTCAE) grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity)