Inclusion Criteria:

The patient must have:

- Histologic or cytologic diagnosis of adenocarcinoma of the colon or rectum.

- Performance status of 0 to 2 on the ECOG Performance Status Scale.

- Standard postoperative adjuvant radiation therapy for rectal cancer is allowed.

- Locally advanced or metastatic disease.

- Must be 18 years of age.

Exclusion Criteria:

The patient must not have:

- Received prior chemotherapy for advanced disease. Prior adjuvant therapy, including
5-FU, is allowed if it has been more than 12 months since the last treatment.

- Received prior treatment with irinotecan in the adjuvant setting.

- Are unable to take vitamin B12 or folic acid.

- Are unable to interrupt aspirin, other nonsteroidal anti-inflammatory drugs, or COX-2
inhibitors for a 5-day period.

- Have a second primary malignancy except carcinoma in situ of the cervix or
nonmelanomatous skin cancer, unless that prior malignancy was diagnosed and
definitively treated at least 5 years previously with no subsequent evidence of
recurrence.