Organ Preservation Program Using Short-Course Radiation & FOLFOXIRI in Rectal Cancer

Inclusion Criteria: * 1\. Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of rectum requiring total mesorectal excision as deemed by multidisciplinary evaluation * 2.At least 18 years of age * 3.For women of childbearing potential or who are not postmenopausal (see Appendix B for Definition of Menopausal Status), a negative urine or serum pregnancy test must be done. Also, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 4 weeks following the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * 4.ECOG 0, 1, or 2 * 5.Ability to understand and the willingness to personally sign the written IRB approved informed consent document. * 6.Patients must have acceptable organ and marrow function as defined below: * Absolute neutrophil count (ANC) \>1,500/uL * Hg \> 8.0 g/dL; if blood transfusion is performed for achieving adequate hemoglobin level, the level should stay above goal for at least 1 week after transfusion * Platelets \>100,000/uL * Total bilirubin \<1.5X normal institutional limits * aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT)(SGPT) \< 3X upper limit of normal * Creatinine \<1.5X upper limit of normal or creatinine clearance (CrCL)\>50 by Cockcroft-Gault * 7 Clinical stage \>T2N0 or low T2N0 rectal cancer (AJCC, 8th ed.) including no metastases based on the following diagnostic workup: * General history and physical examination with DRE (if deemed appropriate by treating physician) within 45 days prior to enrollment * Sigmoidoscopy within 90 days prior to enrollment The following imaging studies are required within 45 days prior to enrollment: * CT chest/abdomen/pelvis * MRI Pelvis Exclusion Criteria: * 1.Prior pelvic RT or chemotherapy for rectal cancer. * 2.Upper T2N0 rectal cancers eligible for sphincter-preservation surgery * 3.Use of other investigational agents. * 4.Ongoing or active infections requiring systemic antibiotic treatment or uncontrolled intercurrent illness including but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * 5.Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Patients with any previous malignancy without evidence of disease for \>3 years will be allowed to enter the trial. * 6.Known hypersensitivity to 5-FU compounds. * 7.Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. (This applies to women who have experienced menarche and have not undergone successful surgical sterilization or are not postmenopausal). Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients with detectable viral loads and/or receiving combination anti-retroviral therapy are excluded from the study. \- 8.Primary unresectable rectal cancer (tumor invading adjacent organs and en bloc resection will not achieve negative margins).