Therefore, the OPTIMA study aims to evaluate 1) whether tumor molecular profiling (e.g. CMS classification, transcriptomics) can predict the efficacy of irinotecan-based systemic treatment and is associated with QoL and OS, and 2) whether UGT1A1-guided dose reduction in UGT1A1 poor metabolizers (PMs) is safe to use, and 3) whether high GUS enzyme activity is associated with GI toxicity, decreased QoL and OS in patients with metastatic or unresectable CRC. Here, UGT1A1 is linked to colorectal carcinoma.