TPS3648^ Background: Several strategies using chemotherapy and molecular targeted drugs are available for the treatment of unresectable metastatic colorectal cancer. Recent and ongoing randomized trials evaluate chemotherapy with bevacizumab or epidermal growth factor receptor (EGFR) inhibitors, but the prior and/or subsequent lines are not fixed and the imbalanced cross-overs will not allow to interpret overall survival. This STRATEGIC-1 trial is a study designed to determine the best sequence of therapy and to define subset populations that will benefit most from one sequence. Methods: This is an ongoing randomized, two-arm, phase III study comparing two multi-line therapeutic strategies in patients wild-type RAS unresectable metastatic colorectal adenocarcinoma, ECOG PS 0-2 and age ≥ 18years. Randomization is stratified by center, GERCOR prognostic score (using PS and LDH level), prior use of oxaliplatin in adjuvant setting and the extent of metastatic disease. Patients (n=474) are randomized (1:1) to ...