Although treatment outcomes for metastatic colorectal cancer (mCRC) have dramatically improved over the past few decades, drug costs have also significantly increased. This study aimed to investigate which first-line treatment regimens for mCRC are actually used (frequency) in Japanese practice and at what cost. We collected data on patients with mCRC who received first-line treatment at 37 institutions of the Japan Clinical Oncology Group Colorectal Cancer Study Group from July 2021 to June 2022, and calculated the cost of regimens. The cost per month of each regimen was estimated based on standard usage, assuming a patient with a weight of 70kg and a body surface area of 1.8m2. We categorized the regimens into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month), and others (<500 000 JPY/month). The study included 1880 participants, 24% of whom were≥75years. Molecular targeted containing regimens were received by 78% of the patients. The most frequently used regimen was the doublet regimen (fluoropyrimidine with either oxaliplatin or irinotecan) plus bevacizumab (43%), followed by doublet plus cetuximab or panitumumab (21%). The cost of molecular targeted drugs-containing regimens (ranging from 85 406 to 843 602 JPY/month) is much higher than that of only cytotoxic drug regimens (ranging from 17 672 to 51 004 JPY/month). About 16% received high-cost treatments that included panitumumab-containing regimens and pembrolizumab (17% of patients aged ≤74years and 11% of patients aged ≥75years). About 16% of mCRC patients received first-line treatment with regimens costing >500 000JPY/month, and molecular targeted drugs being the main drivers of cost.