This is a Phase I dose escalation study to determine how much chemotherapy can be safely administered into the abdomen while experiencing the fewest possible side effects.

There are two common combinations of chemotherapy drugs used to treat cancer of the colon, rectum, or appendix that has spread to the abdomen. One uses 5-fluorouracil (also called 5-FU), leucovorin and oxaliplatin, and is called FOLFOX. The other uses 5-FU, leucovorin, and irinotecan, and is called FOLFIRI. The Food and Drug Administration (FDA) has approved each of these combinations as treatment for colon or rectal cancer. Each is given through the veins.

FOLFOX and FOLFIRI do not work well for tumors growing in the abdominal cavity. The investigators are trying to determine if giving chemotherapy called oxaliplatin directly into the abdominal cavity will have a greater effect on the cancer.

The FDA has approved oxaliplatin to be given to people through their veins to treat advanced colorectal cancer. Giving oxaliplatin directly into the abdomen in this study is experimental and is not approved by the FDA. This study will give the standard chemotherapy FOLFIRI through the veins and oxaliplatin directly into the abdomen. This is the first time intraperitoneal oxaliplatin is being given in combination with FOLFIRI.

Inclusion Criteria:

• Must be 18 years of age or older and capable of providing informed consent indicating awareness of the investigational nature of this trial, in keeping with institutional policy
• Must consent to participate in the trial and have signed an approved informed consent form conforming to institutional policy
• Must have histopathologically or cytologically confirmed colon, rectal or appendiceal adenocarcinoma with synchronous or metachronous peritoneal dissemination of disease.(Stage IV peritoneal based disease only)
• Must have active measurable disease by either abdominal computerized axial tomography (CT)/ Magnetic resonance imaging (MRI) or laparoscopy.

Adequate laboratory values

• Absolute neutrophil count (ANC) > 1200/10*3/uL
• Platelet count > 140,000/10*3/uL
• Total serum bilirubin ≤ 1.5 mg/dl (patients with total bilirubin >1.5 mg/dL are eligible only with Gilbert's syndrome)
• Alkaline phosphatase < 2.5 times the upper limit of normal (ULN) (alkaline phosphatase and AST cannot both exceed the ULN)
• Aspartate aminotransferase (AST) < 1.5 times the ULN (alkaline phosphatase and AST cannot both exceed the ULN)
• Serum renal function parameters (BUN and creatinine) are within normal limits (eGFR) >50)
• Satisfactory cardiopulmonary function (as determined by Physician)
• Patients can have received prior systemic chemotherapy, radiation or surgery
• Patients must be able to undergo placement of an intraperitoneal (IP) catheter and a Port-A Cath, if not already present
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Women of reproductive age and men who are sexually active must be willing to practice effective contraception
• Patients will be allowed to have secondary malignancies as long as they do not require active concomitant treatment