 The aflibercept-5-FU combination has never been evaluated as yet. Aflibercept, at a dose of 4 mgkg, has already been used in combination with 5-FU at the doses used in the simplified LV5FU2 regimen folinic acid 400 mgm2 IV in 90 min, then 5-FU 400 mgm2 IV bolus on D1, followed by continuous perfusion of 5-FU 2,400 mgm2 in 46h 23 as part of the above-mentioned VELOUR trial, evaluating its combination with FOLFIRI simplified LV5FU2 irinotecan. This trial was preceded by a phase I trial validating the doses used 24. It is therefore not necessary to perform a phase I trial if you use the same doses of 5-FU without irinotecan, within the context of a strategy for reducing toxicity in patients to be treated over a long period, and not search for the maximum tolerated dose of the combination. 