Mechanically strong silk fibroin cryogels with two generations of pores were produced by carrying out the cryogelation reactions within the pores of the initial single-network (SN) fibroin cryogels. In this way, cryogels with interpenetrated and interconnected double-(DN), and triple-network (TN) structures were produced from fibroin solutions frozen at -18 degrees C in the presence of butanediol diglycidyl ether crosslinker and N, N, N', N'-tetramethylethylenediamine as a pH regulator. Cryogel scaffolds formed at fibroin concentrations above 25 wt% exhibit a Young's modulus between 66 and 126 MPa, and sustain around 90% compressions under 87-240 MPa stresses. These values are the largest reported so far for fibroin scaffolds and hence the materials have promising applications in bone tissue engineering. We also show that the improvement in the mechanical performance of cryogels after multiple-networking is due to their increased content of fibroin network. Both DN and TN cryogels have two generations of interconnected macropores with diameters 20-30 mm and 3-9 mm. The size of both large and small pores could be adjusted by the relative amounts of fibroin in the network components. (C) 2017 Elsevier Ltd. All rights reserved.