The modular and distributed bioproduction requires continuous flow microreactors that are integrated into efficient separation units that operate on comparable time scales: the two-phase reactive extraction of 5-hydroxymethylfurfural (HMF) by fructose dehydration is an excellent example. Liquid-liquid extraction (LLE) and the fast reaction kinetics in two-phase microchannels can benefit immensely from a downstream microseparator that enables the separation of an HMF-rich organic extract and an aqueous raffinate. Here we show the successful implementation of an effective slot-shaped microseparator for eleven two-phase systems with organic water. The microseparator successfully separates six of these at reasonable flow rates. The ratio of capillary and hydraulic pressure streamlines separation performance qualitatively, while a transition to non-segmented flow patterns correlates with performance degradation. Acids and salts, integral parts of chemistry, significantly increase flow rates for efficient separation and enable a wider range of organic solvents. For the two-phase MIBK / water system, we show a perfect separation performance over a 16-fold variation in the ratio of organic to aqueous flow. Here we also integrate the microseparator and the extractive microreactor into a modular system and achieve an HMF yield of up to 93% – the highest reported fractionated HMF productivity of 27.9 min−1 – with an ultra-short dwell time of 2 s.This unprecedented performance is maintained over a 50-fold fructose concentration range and is stable over time. This microseparator shows a tenfold reduction in the separation time and considerable energy savings compared to conventional decanters. As such, it promises continuous process intensification and modular bioproduction.