Objectives: To describe direct medical costs associated with each line of treatment among metastatic colorectal cancer (mCRC) patients in China. Methods: Electronic medical records between 2011 and 2016 were extracted from 12 tertiary hospitals in China for adult patients who initiated third-line treatment at least nine months before the end of data collection. Direct medical costs included costs of wards, diagnostic tests, surgical procedures, special materials, drugs and others. Costs were assessed by line of treatment, and drug costs were further breakdown for patients receiving chemotherapy alone and those receiving chemo- and biologics-combined therapy. Results: Of the 404 mCRC patients, the mean age was 55 years old and 62% were male. Oxaliplatin- and irinotecan-based regimens dominated first- and second-line treatment, respectively (44 and 37%). From first- to second- to third-line, the proportion of patients receiving targeted biologics increased from 18% at first-line and 12% at second-line to 34% at third-line; median number of treatment cycles reduced from 6 to 4 and to 2. The corresponding mean direct medical costs per person per cycle increased from $2,514 to $2,678 to $5,121. Mean drug costs per cycle increased from $2,314 to $2,673 to $4,316 among patients receiving chemotherapy alone and from $3,245 to $2,717 to $6,533 among patients receiving chemo- and biologics-combined therapy. Conclusions: Before 2017, mCRC patients in China did not receive the maximum benefits of precision medicine breakthroughs. Reduced treatment cycles and increased costs per cycle from first- to third-line suggested poor healthcare resource utilization. With earlier initiation and more treatment cycles, targeted biologics may better demonstrate their effectiveness among Chinese patients. Our findings reflected the urgent need to increase drug accessibility in China before 2017 and underscore that including innovative biologics into Chinese health insurance plans can reduce patients' economic burden and improve the management of mCRC.