For almost 40 years, 5-fluorouracil (5-FU) has been the only useful drug with clinically meaningful activity in metastatic colorectal carcinoma. When the disease progresses or recurs despite bolus 5-FU treatment, the options are limited. Our study shows that 5-FU given by continuous infusion is a viable alternative. Fifty-three patients received continuous infusion 5-FU. The overall response was 9%. Median survival of the entire cohort was 5 months. Patients with partial response and stable disease had median survival duration of 8 and 9 months, respectively. A dose-response relationship was observed. The commonest toxicities were mucositis (34%) and palmar-plantar syndrome (24%). There was no central line-related complication. Continuous infusion 5-FU is an effective "second-line" treatment. Further work is needed to ascertain its role, in comparison with newer agents like irinotecan (CPT-11), and oxaliplatin.