Colorectal cancer (CRC) is one of the most common malignant tumors in adults. Twenty-five percent of patients are not amenable to surgical resection because they have locally advanced or metastatic disease. For these patients, median survival time is between 4 and 13 months, and chemotherapy is used mainly with palliative intent. We conducted this study to evaluate potential prognostic factors for time to progression and survival. A retrospective review of 91 patients with metastatic CRC treated with bolus 5-fluorouracil-based chemotherapy (Mayo Clinic schedule) was performed. Univariate and multivariate analyses of clinical prognostic factors were carried out. Median follow-up time was 53 months (range, 17-107 months). Median time to disease progression was 9.6 months, and median survival time was 15.4 months. Actuarial 5-year survival was 17%. In the univariate analyses, factors predictive of time to progression were visceral metastases, elevated alkaline phosphatase (AP) levels, performance status (PS), and elevated carcinoembryonic antigen (CEA) and CA 19-9 levels. Multivariate analyses confirmed the independent prognostic value of PS and AP levels. In the univariate analyses for survival, significant prognostic factors were visceral metastases, hypoalbuminemia, elevated lactate dehydrogenase levels, elevated AP levels, PS, and elevated CEA and CA 19-9 levels. In the multivariate analyses, only PS, elevated CEA and CA 19-9 levels, and liver involvement retained prognostic significance. This study confirms the prognostic value of PS for both time to progression and survival. AP levels are significantly related to time to progression. Additional factors influencing survival time are elevated tumor marker levels and the existence of liver metastases.