The chemotherapy of metastatic colorectal cancer has demonstrated a symptomatic benefit and a prolongation in survival. The modulation of 5-fluorouracil (5-FU) by leucovorin is the current standard treatment. The best protocols include 5-FU 24 or 48 hour continuous infusion on a weekly or bimonthly schedule. The response rate is about 30%, the median progression-free survival is 6 to 8 months and the median survival 10 to 15 months. The toxicity is moderate. New drugs are available or under evaluation: 5-FU prodrugs, raltitrexed, CPT11, oxaliplatin, trimetrexate. Synergisms with 5-FU allow to consider more effective polychemotherapies.