The efficient synthesis of the platform chemical 5-hydroxymethylfurfural (HMF) is of great significance for the production of downstream value-added bio-based chemicals. Herein, the highly-efficient and continuous synthesis of HMF is demonstrated in micropacked bed reactors (μPBRs) with HND-580. 95.3 % fructose conversion, 90.2 % HMF yield, and 99.3 % HMF extraction efficiency can be achieved within 26.3 s in μPBRs. The space–time yield (STY) of μPBRs is more than two times of magnitude greater than conventional fixed bed reactors (FBRs) and stirred tank reactors (STRs). The organic phase liquid holdup of liquid–liquid system is obtained at the range of 0.82–0.90, which is measured for the first time in μPBRs. The liquid–liquid mass transfer coefficient of μPBRs is 1.68 × 10-2 to 1.68 × 10-1 s−1, which is 1–3 orders of magnitude larger than STRs and packed columns. In addition, a heterogeneous kinetic model for the synthesis of HMF in water-MIBK biphasic system is established in μPBRs. The fructose conversion and HMF yield were predicted and the error was within ± 20 %.