FOLFIRI-aflibercept chemotherapy is indicated in second-line treatment of metastatic colorectal cancer (mCRC) after progression under FOLFOX (±bevacizumab). Nevertheless, its proven therapeutic efficacy in clinical trials was based on partial responses. And to date, only 2 cases of complete response assessed by CT were reported in literature. We report a complete metabolic response assessed by FDG PET/CT in a 50-year-old woman with mCRC treated by FOLFIRI-aflibercept. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.