Therefore, the OPTIMA study will evaluate in patients with advanced CRC: 1) whether tumor molecular profiling can predict the efficacy of irinotecan-based systemic treatment; 2) whether high bacterial GUS enzyme activity is associated with increased gastrointestinal toxicity, decreased QoL and OS; as well as 3) the safety of a 70% irinotecan dose intensity in UGT1A1 poor metabolizers (PMs). The gene discussed is UGT1A1; the disease is colorectal carcinoma.