Background and aims: Bevacizumab-based chemotherapy is a recommended first-line treatment for metastatic colorectal cancer (mCRC). Robust biomarkers with clinical practice applicability have not been identified for patients with this treatment. We aimed to evaluate the prognostic yield of serum midinfrared spectroscopy (MIRS) on patients receiving first-line bevacizumab-based chemotherapy for mCRC. Methods: We conducted an ancillary analysis from a multicentre prospective study (NCT00489697). All baseline serums were screened by attenuated total reflection method. Principal component analysis and unsupervised k-mean partitioning methods were performed blinded to all patients' data. Endpoints were progression-free survival (PFS) and overall survival (OS). Results: From the 108 included patients, MIRS discriminated two prognostic groups. First group patients had significantly lower body mass index ( p = 0.026) and albumin levels ( p < 0.001), and higher levels of angiogenic markers, lactate dehydrogenase and carcinoembryonic antigen ( p < 0.001). In univariate analysis, their OS and PFS were shorter with respective medians: 17.6 vs 27.9 months ( p = 0.02) and 8.7 vs 11.3 months ( p = 0.03). In multivariate analysis, PFS was significantly shorter (HR = 1.74, p = 0.025) with a similar trend for OS (HR = 1.69, p = 0.061). Conclusion: By metabolomic fingerprinting, MIRS proves to be a promising prognostic tool for patients receiving first-line bevacizumab-based chemotherapy for mCRC.