For many years, the treatment of metastatic colorectal cancer was restricted to 5FU and its biomodulation. Oxaliplatin and irinotecan, combined with continuous infusion of 5FU significantly improved response rate, progression-free survival and overall survival. Folfox4 (oxaliplatin and LV5FU2) is more active than LV5FU2 alone, and has shown also a superiority over IFL (irinotecan, 5FU bolus, leucovorin). Combining a 2-line strategy (Folfox then Folfiri or the reverse sequence), a median overall survival over 20 months has been reached. In the Optimox1 trial, comparing Folfox4 until progression and Folfox7 followed by a maintenance of simplified LV5FU2 and reintroduction of Folfox7, a similar response rate, progression-free survival and overall survival is observed. The next trial, Optimox2, is testing a "stop and go" strategy, in order to reduce the number of cycles and the cumulative toxicity. Combinations of capecitabine and oxaliplatine are also promising. The next step will come from the two new targeted therapies in metastatic colorectal cancer, directed against EGFR and VEGF.