QoL measures consistently favored the Doublet arm, showing improved health status and reduced deterioration risk.<h4>Conclusions</h4>This NAUTICAL CRC Phase II study showed that the combination of encorafenib and cetuximab offers significant clinical benefits, improving PFS and OS, while providing manageable safety and important QoL advantages, making it a valuable treatment option for Chinese patients with previously treated BRAF<sup>V600E</sup> mutant mCRC.<h4>Trial registration</h4>Clinical study registration number: NCT05004350. This evidence concerns the gene BRAF and colorectal carcinoma.