$bufsize = length $buffer;
# Make sure it's an integer multiple of 8 by reducing by any remainder
$bufsize -= $bufsize % 8;
#you could copy substr($buffer, 0, $bufsize) if you wanted/needed to
syswrite (OUTFILE, $buffer, $bufsize);
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"I intend then to chain and blowfish it before syswriting the buffer back out to the encrypted file.", the OP said. Blowfish only works on 8 bytes of data at a time, so the OP is looking for an efficient method of dividing a string into 8 byte segments.

cos Crypt::Blowfish works with 8 byte blocks. The disk reads and writes I'm doing in 64k chunks which seems about optimum. I'm then splitting the 64k buffer into 8 byte lumps for Blowfish.

I suspect you will do no worse letting Perl handle the buffering for you:

$/ = \8; # Read 8-byte records. Behind the scenes, Perl will do buffer
+ing of reads.
$out_buffer .= blowfishify($_) while <INFILE>;
print OUTFILE $out_buffer;
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Alternatively, you could (with a sufficiently modern Perl) read from your buffer as if it were a filehandle, using the same $/ = \8 trick.

open BUF, '<', \$buffer or die "$!: Could not open buffer\n";
$/ = \8;
$out_buffer .= blowfishify($_) while <INFILE>;
print OUTFILE $out_buffer;
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They're tidier ways of doing what you want, but you'd have to try them to see whether they buy or lose you any efficiency. My guess is that the I/O isn't going to be the bottleneck, anyway; the encryption is.

---

Caution: Contents may have been coded under pressure.

I thought there might be a way of reusing the existing code in Crypt::CBC, so I took a peek. Not only can code from Crypt::CBC be reused, Crypt::CBC already does what you want! The following encrypts:

use Crypt::CBC;

my $cipher = Crypt::CBC->new(...);

open(INFILE, '<', 'BIG_FILE.txt')
   or die("Unable to open input file: $!");

open(OUTFILE, '>', 'BIG_FILE.enc')
   or die("Unable to create output file: $!");

$cipher->start('encrypting');
while (read(INFILE, $buffer, 65536)) {
   print OUTFILE $cipher->crypt($buffer);
}
print OUTFILE $cipher->finish;
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The following decrypts:

use Crypt::CBC;

my $cipher = Crypt::CBC->new(...);

open(INFILE, '<', 'BIG_FILE.enc')
   or die("Unable to open input file: $!");

open(OUTFILE, '>', 'BIG_FILE.txt')
   or die("Unable to create output file: $!");

$cipher->start('decrypting');
while (read(INFILE, $buffer, 65536)) {
   print OUTFILE $cipher->crypt($buffer);
}
print OUTFILE $cipher->finish;
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while (my $bufsize = read(INFILE, my $eight_byte_chunk, 8)) {
   ...[ Add padding    ]...
   ...[ Encrypt        ]...
   ...[ Merge with IV  ]...
   ...[ Compute new IV ]...
   write(OUTFILE, $eight_byte_chunk, 8);
}
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Because I thought read would be slower than sysread and the 8 byte buffer would result in a lot of disk thrashing compared to 64k buffer

the 8 byte buffer would result in a lot of disk thrashing compared to 64k buffer

And there shouldn't be any disk trashing because read and write are buffered. The size of the buffer isn't 8 bytes as you claim, but rather a multiple of the size of a disc sector. The disk is not accessed every time read and write is called.

Because I thought read would be slower than sysread

sysread + syswrite + manual buffering in Perl
should be slower than
read + write + well tested buffering in C

Note that I didn't say my way is faster, just that it might be. Benchmark to find out which is faster on your system.