Background: As the incidence of early-onset mCRC continues to rise, evidence is emerging for the use of more aggressive treatment in the front-line setting in patients aged < 50 years (yrs). Although the superior efficacy of the multiagent chemotherapy FOLFOXIRI+bevacizumab (triplet+bev) over doublet regimens (FOLFOX or FOLFIRI+bev) is well documented, it is commonly associated with increased toxicity. Contemporary data are needed on triplet+bev use by age group in the US, which may help tailor treatment in patients with early-onset mCRC. Methods: This was a retrospective, observational cohort study using Optum Oncology Electronic Health Records data between 2010 and 2021. Use of triplet+bev and subsequent treatments were reported by age group (18–49, 50–64, ≥65 yrs) among newly diagnosed patients with mCRC. Baseline demographic and clinical characteristics data for patients receiving triplet+bev and regorafenib as a subsequent treatment were collected. Results: Among 36,053 eligible patients with mCRC diagnosed between 2010 and 2021, 13.8% were aged 18–49 yrs, 36.4% 50–64 yrs, and 49.8% ≥65 yrs at the time of diagnosis. The proportion of patients receiving triplet+bev was higher in age groups 18–49 yrs (4.0%) and 50–64 yrs (3.4%) vs ≥65 yrs (1.5%). Between 2010 and 2020, the proportion of patients receiving triplet+bev changed from 1.5% to 4.2% in age group 18–49 yrs, from 3.1% to 2.6% in 50–64 yrs, and from 1.1% to 1.2% in ≥65 yrs. Over a median 20-month follow-up period, 58.0% of patients in age groups 18–49 and 50–64 yrs, and 53.7% of patients in age group ≥65 yrs, received a new treatment after triplet+bev. In the overall cohort, the most common new treatment after triplet+bev was regorafenib (20.7%), received by 18.2% of patients in age group 18–49 yrs, 22.7% in 50–64 yrs, and 19.2% in ≥65 yrs. Other new subsequent treatments in the overall cohort included trifluridine/tipiracil (17.1%) and cetuximab (16.3%), with a similar trend seen among all age groups. Across age groups, triplet+bev recipients were more likely to be male, obese, resident in the Midwest or Northeast, and have distant metastases, and less likely to have colorectal surgical resection prior to mCRC diagnosis. Patients in age group 18–49 yrs subsequently receiving regorafenib were more likely to be obese and less likely to have Charlson Comorbidity Index ≥3, distant metastases, and colorectal surgical resection before mCRC diagnosis vs those who did not receive regorafenib. Conclusions: Our study shows that, recently, triplet+bev use has increased in patients with mCRC, particularly in those aged < 50 yrs. Chemotherapy-free treatments may be an option for these patients beyond the first-line setting. While regorafenib is typically used in third or later lines, these real-world data suggest it is often a preferred option following triplet+bev treatment.