Introduction Young-onset colorectal cancer (YOCR) is increasing. This study aimed to determine the difference between advanced YOCR and non-YOCR patient outcomes. Methods We retrospectively included patients with recurrent/metastatic colorectal cancer treated with palliative systemic therapy between 2016 and 2018. Diagnosis at < 50 years was defined as YOCR. Targeted sequencing was used to assess the mutational status. Results Among the 969 patients included, 210 (21.7%) were YOCR. The median progression-free survival with first-line chemotherapy (PFS1) was 9.7 vs 9.4 months ( P = .755), and the median overall survival (OS) was 25.9 vs 22.3 months ( P = .581) in the YOCR and the non-YOCR group, respectively. However, the youngest patients diagnosed at < 30 years showed poorer survival outcomes (median PFS1, 3.9 months; median OS, 8.6 months) compared with other age groups. PFS1 did not differ between YOCR and non-YOCR by choice of treatment regimen. Among the 340 patients with targeted sequencing results, YOCR had fewer APC mutations (61% vs 80%), but had similar KRAS (53% vs 48%), NRAS (7% vs 3%), and BRAF class I mutations (4% vs 6%). The median tumor mutational burden (TMB) was 10.9 vs 12.5 mut/Mb in YOCR and non-YOCR patients, respectively ( P = .064). TMB increased with age in tumors with high microsatellite instability (Pearson’s R = .69, P = .028), but not in microsatellite-stable tumors ( R = .02, P = .658). Conclusions Survival outcomes with palliative systemic therapy were similar between recurrent/metastatic YOCR and non-YOCR with an age cut-off of 50 years. However, patients diagnosed at < 30 years of age showed poorer outcomes compared with other age groups.