TAS-102 With Concurrent Radiation for the Treatment of Untreated Resectable Stage II-III Rectal Cancer

Inclusion Criteria: * All races and ethnic groups will be included * Histologically confirmed diagnosis of adenocarcinoma of the rectum * Clinical stage II (T3-4aN0M0) and stage III (T1-4aN1+M0) based on MRI * Resectable primary rectal tumor at baseline * No evidence of distant metastases * No prior pelvic radiation therapy * No prior chemotherapy or surgery for rectal cancer * No active infections requiring systemic antibiotic treatment (oral antibiotics are acceptable at the discretion of the treating physician) * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Leukocytes \>= 3,000/uL * Absolute neutrophil count \>= 1,500/uL * Hemoglobin \>= 9.0 gm/dL * Platelets \>= 100,000/uL * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN) * Creatinine within normal institutional limits, OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal * Female participants of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A female of childbearing potential is defined of one who is biologically capable …